This proposal concerns three separate but related subjects. They represent approaches to a better understanding of human immune responses in general, and cellular immunity, in particular. An ongoing interest consists in the analysis of the cellular mechanisms involved in the control of delayed hypersensitivity using desensitized guinea pigs as a model, and comparing the immunological changes occurring in these animals with the immunological aberrations that can be detected in a number of human diseases associated with energy and other disturbances of cell mediated immunity. We are currently studying and comparing to changes noted in our animal model, patients with depressed cell mediated immunity who have sarcoidosis, Crohn's disease, alcoholic liver disease, the nephrotic syndrome, and chronic renal failure. The second aspect of this work concerns the developmental, regulatory, and pathological aspects of humoral and cellular immune responses. Recently this has led us to detailed investigation of the relationship between IgE levels and T cell function. We are also studying the distribution and function of T and B lymphocytes in a number of immune deficiency states and looking at the in vivo and in vitro effects of transfer factor on the function of the lymphocytes from such patients. The third study consists of analysis of the dose-dependent effect of immunosuppressive agents used in the treatment of cancer and transplantation problems. Recently, emphasis has been given to the early detection of transplantation rejection episodes by repeated observations of a large number of in vitro correlates of cell mediated immunity in patients who have received kidney transplants.